ARDS is a frequently lethal pulmonary process that occurs in approximately 150,000 patients each year. Total liquid ventilation (TLV), in which the lungs are filled with perfluorocarbon and ventilated with a device which oxygenates and removes carbon dioxide from the perfluorocarbon, has great potential to treat effectively patients with ARDS. The clinical principal investigator has been performing studies in liquid ventilation over the last 8 years. Through our laboratory effort, we have generated data that demonstrate the efficacy of TLV in improving gas exchange, pulmonary function, and oxygen delivery, as well as in reducing acute lung injury. The bioengineering principal investigator has been performing studies in biofluid mechanics and transport of the pulmonary system for many years. This proposal addresses several fundamental physiological and bioengineering issues that underlie the progress toward establishing TLV as a clinical tool: 1) the optimal means for administering the liquid into the lungs; 2) the effect of ventilation parameters upon gas exchange; and 3) the expiratory flow limitation which restricts the effectiveness of the technique. The current research proposal is, therefore, directed at developing a new partnership between a clinician scientist and a bioengineer in the investigation of these issues which involve principles of fluid delivery and distribution, gas transport, and flow limitation during expiration. Specifically, our investigation will assess the distribution of the perfluorocarbon with regard to rate of fill, position during filling, and the characteristics of the perfluorocarbon. Secondly, we intend to investigate and to model the parameters which affect gas exchange during TLV, such as tidal volume, respiratory rate, and lung distension, and to model local flow patterns within the airways and alveoli. Finally, we plan to assess the relationship of flow limitation during expiration to the rate of flow and the state of inflation of the lungs and to investigate strategic means of manipulating parameters which determine flow limitation. A thorough understanding of these issues and solutions to these problems will be critical to the clinical application of this new and exciting technology.